Ceramide Signaling in Cannabinoid Action

Ismael Galve-Roperh, Cristina Sánchez, Teresa Gómez del Pulgar, Guillermo Velasco, Daniel Rueda, Cristina Blázquez and Manuel Guzmán

Cannabinoids, the active components of Cannabis sativa (marijuana) and their endogenous counterparts, exert their effects by binding to specific G_i/o-protein-coupled receptors that modulate adenylyl cyclase, ion channels and extracellular signal-regulated kinase. Recent resear...

Ceramide-Mediated Receptor Clustering

Erich Gulbins and Heike Grassmé

Many stress or pro-apoptotic stimuli such as irradiation, heat shock, UV light, bacterial or viral infections, ligation of CD95 or the tumor necrosis factor receptor have been shown to activate the acid and N-SMase to release ceramide from SM or to stimulate the de novo synthesis of cera...

Characteristics and Biological Functions of TRAF6

Jun-ichiro Inoue, Jin Gohda and Taishin Akiyama

TRAF6 is divergent from other members of the TRAF family. Therefore, TRAF6 was expected to play physiological roles distinct from those of other TRAFs. In this chapter, we focused on the physiological functions specific to TRAF6 but not other TRAFs in immune system, formation of skin appendi...

Critical Experiments to Determine if Early Nutritional Influences on Epigenetic Mechanisms Cause Metabolic Imprinting in Humans

Robert A. Waterland

Metabolic imprinting occurs when nutritional influences during critical periods of development cause specific metabolic adaptations that persist to adulthood. Epigenetic mechanisms, which regulate the broad diversity of tissue-specific gene expression, are established during development and large...

Crosstalk of Ceramide with Cell Survival Signaling

Toshiro Okazaki, Tadakazu Kondo, Mitsumasa Watanabe, Yoshimitsu Taguchi and Takeshi Yabu

In addition to the involvement of ceramide in pro-apoptotic signaling, the role of ceramide as an anti-apoptotic, or cell survival signal, has also been investigated. So far, many anti- apoptotic molecules such as protein kinase C (PKC), mitogen-activated protein (MAP) kinase, phospholip...

Developmental Origins of Cardiovascular Disease, Type 2 Diabetes and Obesity in Humans

Caroline H.D. Fall

Fetal growth restriction and low weight gain in infancy are associated with an increased risk of adult cardiovascular disease, type 2 diabetes and the Metabolic Syndrome. The fetal origins of adult disease hypothesis proposes that these associations reflect permanent changes in metabolism, body c...

Developmental Programming of Cardiovascular Dysfunction

Lucilla Poston, James A. Armitage and Paul D. Taylor

Population based studies of developmental programming of adulthood cardiovascular disease have implied associations between intrauterine growth restriction and a range of adulthood indices of cardiovascular dysfunction and risk. Whilst the emphasis has been on the programming of hypertension, the...

Dual Regulation with Ser/Thr Kinase Cascade and a His/Asp TCS in Myxococcus xanthus

Sumiko Inouye and Hirofumi Nariya

Fruiting body development of Myxococcus xanthus is propelled by temporal gene expression directed via stage‑specific intercellular signaling pathways. M. xanthus exhibits social behaviors during its complex life cycle and is a potential source for production of natural products such as seconda...

Fas Induced Necrosis

Tom Vanden Berghe, Nele Festjens, Michael Kalai, Xavier Saelens and Peter Vandenabeele

Fas/CD95 is an important regulator of cell death in development and homeostasis of the immune system. Apoptosis is the most frequently observed type of cell death induced by Fas. It is characterized by cell shrinkage and nuclear fragmentation, while organelles and the plasma membrane retain their...

Fas-Activation, Development and Homeostasis of T Cells

Georg Hacker

Fas (APO-1/CD95) is found on various cells of the immune system where its expression depends on differentiation and activation status of the cells. Analysis of the function of Fas on T lymphocytes has been the objective of many studies. Like in most cells carrying Fas, ligation by antibodies or F...

Fas-More Than an Apoptosis Inducer

Harald Wajant

Fas (Apo-1 or CD95) and its corresponding ligand FasL (CD95L) are representative members of the TNF receptor and TNF ligand family that have been implicated in a variety of apoptotic processes, involved in T-cell induced cytotoxicity, activation-induced cell death, immune privilege, tumor surveil...

FasL and Fas in Liver Homeostasis and Hepatic Injuries

Maria Eugenia Guicciardi and Gregory J. Gores

Fas is a death receptor expressed by every cell type in the liver. Engagement of Fas with its cognate ligand, Fas ligand (FasL), initiates a signaling cascade resulting in cell death by apoptosis. Fas plays a central role in maintaining liver homeostasis by contributing to the elimination of sene...

FasL and Fas: Typical Members of the TNF Ligand and Receptor Family

Anja Krippner-Heidenreich and Peter Scheurich

The membrane receptor Fas is one of the central members of the TNF receptor superfamily, representing the prototype of an apoptosis inducer. Its cognate ligand, FasL, is expressed as a type II transmembrane protein, but also exists as a soluble molecule. Typical for all members of the receptor su...

FasL-Independent Activation of Fas

Faustino Mollinedo and Consuelo Gajate

Fas death receptor (also named CD95 or APO-1) is physiologically activated through binding to its cognate ligand, FasL. Fas/FasL interaction induces oligomerization and aggregation of Fas receptor, leading eventually to apoptosis after protein-protein interactions with adaptor and effector protei...

Forward Genetic Analysis of TLR Pathways: A Shared System for the Detection of Endotoxin and Viral Infection

Bruce Beutler, Kasper Hoebe, Philippe Georgel, and Xin Du

The mammalian Toll-like receptors (TLRs) were first recognized as innate immune sen sors when it was discovered that TLR4 is the key component of the mammalian endot oxin (lipopolysaccharide; LPS) receptor. This determination was made when a spontaneous mouse mutation, Lps, was positionally clone...

GCAPs: Ca²⁺Sensitive Regulators of retGC

Wojciech A. Gorczyca and Izabela Sokal

Lowered concentration of Ca²⁺ ions, resulting from illumination of the photoreceptor cell, is the signal for resynthesis of cGMP by retinaspecific guanylyl cyclase (retGC). This Ca²⁺ dependent activation of retGC is mediated by Ca²⁺ binding proteins named...

Genetic Susceptibility to Infectious Diseases Linked to NRAMP1 Gene in Farm Animals

Judith Caron, Danielle Malo, Christopher Schutta, Joe W. Templeton and L. Garry Adams

Comparative genomics is playing a pivotal role in the genetic dissection of complex traits such as infectious diseases resistance. Using mouse models of infection, natural resistance associated macrophage protein 1 (Nramp1) was shown to have a critical role in innate resistance to infection with ...

GTPases in Semaphorin Signalling

A hallmark of semaphorin receptors is their interaction with multiple GTPases. Plexins, the signal transducing component of semaphorin receptors, directly associate with several GTPases. In addition, they not only recruit guaninine nucleotide exchange factors (GEFs) and GTPase activating proteins (G...

Guanylate Cyclase Activating Proteins, Guanylate Cyclase and Disease

Richard J. Newbold, Evelyne C. Deery, Annette M. Payne, Susan E. Wilkie, David M. Hunt and Martin J. Warren

_A range of cone and conerod dystrophies (CORD) have been observed in man, caused by mutations in retinal guanylate cyclase 1 (RetGC1) and guanylate cyclase activating protein 1 (GCAP1). The CORD causing mutations in RetGC1 are located at a mutation "hot spot" within ...

Hypoxia, Fetal Growth and Developmental Origins of Health and Disease

Dino A. Giussani

The compelling evidence linking small size at birth with later cardiovascular disease, ` obtained from epidemiological studies of human populations of more than a dozen countries,1 has clearly renewed and amplified a clinical and scientific interest into the determinants of fetal growth, bir...

Inhibitors Targeting Two‑Component Signal Transduction

Takafumi Watanabe, Ario Okada, Yasuhiro Gotoh and Ryutaro Utsumi

A two‑component signal transduction system (TCS) is an attractive target for antibacterial agents. In this chapter, we review the TCS inhibitors developed during the past decade and introduce novel drug discovery systems to isolate the inhibitors of the YycG/YycF system, an essential TCS for b...

Insights into the Modulation of Ceramide Metabolism by Naturally Occurring and Synthetic Sphingolipid Analogs as Monitored by Electrospray Tandem Mass

Alfred H. Merrill, M. Cameron Sullards, Jeremy C. Allegood, Elaine Wang, Stephen C. Linn, Lindsay Andras, Dennis C. Liotta, Michaela Hartl and Hans-Ulrich Humpf

Fumonisins have considerable structural similarity to sphinganine, as illustrated in Figure 1 for one of the most prevalent species (fumonisin B₁, FB₁) and its backbone aminopentol (AP₁). Fumonisins inhibit ceramide synthase, and perturbation of sphingolipid me...

Interleukin-1 Receptor/Toll-like Receptor Signaling

Harald Wajant, Peter Scheurich and Frank Henkler

Upon stimulation Interleukin-1 receptor (IL-1R), the related IL-18R as well as the Toll-like receptors (TLRs), trigger signaling pathways that activate the transcription factors, nuclear factor ?B (NF-?B), activator protein 1 (AP1) and interferon regulatory factor 3 (IRF-3). All members of the IL...

Intracellular Kinases in Semaphorin Signalling

Originally identified as collapse-inducing and repellent proteins for neuronal processes, Semaphorins are now implicated in a diverse array of cellular responses, contributing not only to embryonic development, but also to the maintenance of tissue integrity in the adult organism. In addition, Semap...

Intracellular Targeting of Rho Family GTPases: Implications of Localization on Function

David Michaelson, Mark Rush and Mark R. Philips

Rho proteins are Ras-related GTPases that regulate a wide variety of cellular processes. More than fifteen mammalian Rho proteins have been described including RhoA-E, G and H, Rac1-3, two isoforms of Cdc42hs, and TC10. Originally identified based on their sequence homology to Ras, a great deal o...